Age-related macular degeneration (AMD) is one of the most common forms of blindness in people over the age of 65. Currently, there is no effective treatment for most patients with AMD, a disease that often results in permanent damage to photoreceptors, but spares most retinal ganglion cells (RGCs) and second-order neurons, such as bipolar and horizontal cells. Similarly, other diseases such as retinitis pigmentosa (RP) cause visual impairment and blindness due to loss of photoreceptors.
Inherent to the power of the human visual system is the ability to transduce light by individual photoreceptors, thus making it a high-resolution image capture system. Several groups worldwide have carried out clinical experiments to determine if electrically stimulating retinal cells, the optic nerve bundle or cells of the visual cortex with microelectrode arrays can generate phosphenes (i.e. sensations of light) in individuals impaired with AMD. These trials have shown that by electrically stimulating neurons with a microelectrode array, blind individuals can indeed recognize a simple pattern such as a horizontal or vertical line. Although these trials have demonstrated that vision is recoverable in a limited fashion, major challenges remain. Due to the size and difficulties in placement of most available electrodes, imprecise electric field stimulation extending over long distances (several cell-body diameters) is used to depolarize neurons. In addition, such methods often require excessive stimulation, which may be harmful, leading to inflammation of the stimulated region and gliosis.
The limitations in using electrical stimulation warrant the need for other methodologies that do not use electrical stimulation, and more closely mimic physiological stimulation. The natural method of stimulation employs biologically active molecules that at very low concentrations become bound to neuronal receptors resulting in transduced signals, a process known as synaptic transmission. Normally, photoreceptors chronically secrete these biologically active molecules in the dark. When the photoreceptors sense light, they reduce their secretion of these molecules. Downstream neurons respond to this change by changing their polarization and producing electrical signals that are transmitted to other neurons. In response to visual cues, specific neurons are activated to generate an accurate pattern of signals that are sent to the brain for interpretation.
Thus, there is a need in the art for alternative methods and devices that will allow for controlled stimulation of neurons in a more precise and physiologically relevant manner, with constitutive activation in the dark, and reduction in activation in response to light. By allowing for control of one or a few neurons in relation to an external stimulus one can more closely mimic the natural way neuronal cells are stimulated and transmit signals to the brain to permit a visual image or other information.